Sex-, species-, and chain length-dependent renal elimination is the hallmark of mammalian elimination of perfluorocarboxylates (PFCAs) and has been extensively studied for almost 30 years. In this review, toxicokinetic data of PFCAs (chain lengths ranging from 4 to 10) in different species are compared with an emphasis on their relevance to renal elimination. PFCAs vary in their affinities to bind to serum albumins in plasma, which is an important factor in determining the renal clearance of PFCAs. PFCA-albumin binding has been well characterized and is summarized in this review. The mechanism of the sex-, species-, and chain length-dependent renal PFCA elimination is a research area that has gained continuous interest since the beginning of toxicological studies of PFCAs. It is now recognized that organic anion transport proteins play a key role in PFCA renal tubular reabsorption, a process that is sex-, species-, and chain length-dependent. Recent studies on the identification of PFCA renal transport proteins and characterization of their transport kinetics have greatly improved our understanding of the PFCA renal transport mechanism at the molecular level. A mathematical representation of this renal tubular reabsorption mechanism has been incorporated in physiologically based pharmacokinetic (PBPK) modeling of perfluorooctanoate (PFOA). Improvement of PBPK models in the future will require more accurate and quantitative characterization of renal transport pathways of PFCAs. To that end, a basolateral membrane efflux pathway for the reabsorption of PFCAs in the kidney is discussed in this review, which could provide a future research direction toward a better understanding of the mechanisms of PFCA renal elimination.

An exposure assessment and risk characterization was conducted to better understand the potential human health significance of trace levels of perfluorooctanoate (PFO) detected in certain consumer articles. PFO is the anion of perfluorooctanoic acid (PFOA). Concentrations of PFO in the consumer articles were determined from extraction tests and product formulation information. Potential exposures during consumer use of the articles were quantified based on an assessment of behavior patterns and regulatory guidance. Health benchmarks were developed and then compared to the exposure estimates to yield margins of exposure (MOEs). A simple one-compartment model was also developed to estimate contributions of potential consumer exposures to PFO concentrations in serum. While there are considerable uncertainties in this assessment, it indicates that exposures to PFO during consumer use of the articles evaluated in this study are not expected to cause adverse human health effects in infants, children, adolescents, adult residents, or professionals nor result in quantifiable levels of PFO in human serum.

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